The carbostyril derivatives of formula (1) or salts thereof and the process for the preparation thereof are disclosed in JP-63-20235-B. And it is known that the carbostyril derivatives (1) have platelet aggregation inhibitory action, phosphodiesterase (PDE) inhibition action, antiulcer, hypotensive action and antiphlogistic action, and are useful as an antithrombotic agent, a drug for improving cerebral circulation, an antiinflammatory agent, an antiulcer drug, an antihypertensive drug, an antiasthmatic drug, a phosphodiesterase inhibitor, etc.
In addition, JP-9-157170-A reports that the carbostyril derivative may be useful as an agent for promoting hepatocyte growth factor (HGF) production. Therefore, the hepatocyte growth action thereof is expected to be useful in the case of treating a disease such as fulminant hepatic failure or promoting the liver regeneration after hepatectomy.
These days, an interest in metabolic syndrome has been increasing. With regard to the evaluation of the syndrome, visceral fat is adopted as one of the criteria thereof. Amongst the visceral fat, especially an interest in fatty liver is increasing. Fatty liver is in a condition that fat is built up in the liver, which causes little subjective symptom. However, the condition could get worse when left untreated, and not a few patients suffering from fatty liver may progress in hepatitis, cirrhosis and liver cancer.
Fatty liver can be roughly classified into alcoholic fatty liver and non-alcoholic fatty liver. As patients of metabolic syndrome increase, there is increasing interest in non-alcoholic steatohepatitis (NASH) in Japan that is a disease of fatty liver accompanied with symptoms of necrosis of hepatocyte, inflammation, and/or fibril formation, which affects even non-drinkers. Although the cause of NASH has not been sufficiently clarified yet, it is thought that fatty liver may be one of the causes at least. Therefore, a strict nutrition therapy is important for the treatment thereof, and drug therapy is also considered for intractable symptom (M. Yoneda, et al., Folia Pharmacologica Japonica, Vol. 128 (2006), No. 4 235-238).
Thus, fatty liver has seriously critical factors to progress toward severe cases, however, there are few effective medicaments for preventing and treating fatty liver. It has been still desired to develop an effective medicament for fatty liver, especially NASH whose cause has not been sufficiently clarified yet and non-alcoholic fatty liver which might progress toward NASH.